Andrea Kobiella

Nicotine Dependence Is Characterized by Disordered Reward Processing in a Network Driving Motivation

BACKGROUND Drug addiction is characterized by an unhealthy priority for drug consumption with a compulsive, uncontrolled drug-intake pattern due to a disordered motivational system. However, only some individuals become addicted, whereas others maintain regular but controlled drug use. Whether the transition occurs might depend on how individuals process drug relative to nondrug reward. METHODS We applied functional magnetic resonance imaging to measure mesocorticolimbic activity to stimuli predicting monetary or cigarette reward, together with behavioral assessment of subsequent motivation to obtain the respective reward on a trial-by-trial basis, in 21 nicotine-dependent and 21 nondependent, occasional smokers. RESULTS Occasional smokers showed increased reactivity of the mesocorticolimbic system to stimuli predicting monetary reward relative to cigarette reward and subsequently spent more effort to obtain money. In the group of dependent smokers, we found equivalent anticipatory activity and subsequent instrumental response rates for both reward types. Additionally, anticipatory mesocorticolimbic activation predicted subsequent motivation to obtain reward. CONCLUSIONS This imbalance in the incentive salience of drug relative to nondrug reward-predicting cues, in a network that drives motivation to obtain reward, could represent a central mechanism of drug addiction.

(Still) longing for food: Insulin reactivity modulates response to food pictures

Overweight and obesity pose serious challenges to public health and are promoted by our food‐rich environment. We used functional magnetic resonance imaging (fMRI) to investigate reactivity to food cues after overnight fasting and following a standardized caloric intake (i.e., a 75 g oral glucose tolerance test, OGTT) in 26 participants (body mass index, BMI between 18.5 and 24.9 kg m−2). They viewed pictures of palatable food and low‐level control stimuli in a block design and rated their current appetite after each block. Compared to control pictures, food pictures activated a large bilateral network typically involved in homeostatically and hedonically motivated food processing. Glucose ingestion was followed by decreased activation in the basal ganglia and paralimbic regions and increased activation in parietal and occipital regions. Plasma level increases in insulin correlated with cue‐induced appetite at the neural and behavioral level. High insulin increases were associated with reduced activation in various bilateral regions including the fusiform gyrus, the superior temporal gyrus, the medial frontal gyrus, and the limbic system in the right hemisphere. In addition, they were accompanied by lower subjective appetite ratings following food pictures and modulated the neural response associated with it (e.g., in the fusiform gyrus). We conclude that individual insulin reactivity is critical to reduce food‐cue responsivity after an initial energy intake and thereby may help to counteract overeating. Hum Brain Mapp 34:2367–2380, 2013.

Fasting levels of ghrelin covary with the brain response to food pictures

Ghrelin figures prominently in the regulation of appetite in normal‐weighed individuals. The apparent failure of this mechanism in eating disorders and the connection to addictive behavior in general demand a deeper understanding of the endogenous central‐nervous processes related to ghrelin. Thus, we investigated processing of pictures showing palatable food after overnight fasting and following a standardized caloric intake (i.e. a 75‐g oral glucose tolerance test) using functional magnetic resonance imaging and correlated it with blood plasma levels of ghrelin. Twenty‐six healthy female and male volunteers viewed food and control pictures in a block design and rated their appetite after each block. Fasting levels of ghrelin correlated positively with food‐cue reactivity in a bilateral network of visual processing‐, reward‐ and taste‐related regions, including limbic and paralimbic regions. Notably, among those regions were the hypothalamus and the midbrain where ghrelin receptors are densely concentrated. In addition, high fasting ghrelin levels were associated with stronger increases of subjective appetite during the food‐cue‐reactivity task. In conclusion, brain activation and subjective appetite ratings suggest that ghrelin elevates the hedonic effects of food pictures. Thereby, fasting ghrelin levels may generally enhance subjective craving when confronted with reward cues.

The discrimination of angry and fearful facial expressions in 7-month-old infants: An event-related potential study

The important ability to discriminate facial expressions of emotion develops early in human ontogeny. In the present study, 7-month-old infants’ event-related potentials (ERPs) in response to angry and fearful emotional expressions were measured. The angry face evoked a larger negative component (Nc) at fronto-central leads between 300 and 600 ms after stimulus onset when compared to the amplitude of the Nc to the fearful face. Furthermore, over posterior channels, the angry expression elicited a N290 that was larger in amplitude and a P400 that was smaller in amplitude than for the fearful expression. This is the first study that shows that the ability of infants to discriminate angry and fearful facial expressions can be measured at the electrophysiological level. These data suggest that 7-month-olds allocated more attentional resources to the angry face as indexed by the Nc. Implications of this result may be that the social signal values were perceived differentially, not merely as “negative”. Furthermore, it is possible that the angry expression might have been more arousing and discomforting for the infant compared with the fearful expression.

Alcohol-Induced Impairment of Inhibitory Control Is Linked to Attenuated Brain Responses in Right Fronto-Temporal Cortex

BACKGROUND A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. METHODS We measured inhibitory control in 50 young adults with a stop-signal task during functional magnetic resonance imaging. In a single-blind placebo-controlled cross-over design, all participants performed the stop-signal task once under alcohol with a breath alcohol concentration of .6 g/kg and once under placebo. In addition, alcohol consumption was assessed with a free-access alcohol self-administration paradigm in the same participants. RESULTS Inhibitory control was robustly decreased under alcohol compared with placebo, indicated by longer stop-signal reaction times. On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. CONCLUSIONS We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans, which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control might enhance alcohol consumption in young adults, which might promote future alcohol problems.

Balancing reward and work: anticipatory brain activation in NAcc and VTA predict effort differentially.

Complex decision-making involves anticipation of future rewards to bias effort for obtaining it. Using fMRI, we investigated 50 participants employing an instrumental-motivation task that cued reinforcement levels before the onset of the motor-response phase. We extracted timecourses from regions of interest (ROI) in the mesocorticolimbic system and used a three-level hierarchical model to separate anticipatory brain responses predicting value and subsequent effort on a trial-by-trial basis. Whereas all ROIs scaled positively with value, higher effort was predicted by higher anticipatory activation in nucleus accumbens (NAcc) but lower activation in ventral tegmental area/substantia nigra (VTA/SN). Moreover, anticipatory activation in the dorsal striatum predicted average effort whereas higher activation in the amygdala predicted above-average effort. Thus, anticipatory activation entails the appetitive drive towards reinforcement that requires effort in order to be obtained. Our results support the role of NAcc as the main hub supported by the salience network operating on a trial-by-trial basis, while the dorsal striatum incorporates habitual responding.

Acute and chronic nicotine effects on behaviour and brain activation during intertemporal decision making

Previous studies demonstrated higher discount rates for delayed rewards in smokers than non‐smokers. We performed this study to determine whether those differences in intertemporal choice are due to pharmacological effects of nicotine and to track related brain regions. Thirty‐three non‐smokers and 27 nicotine‐dependent smokers underwent functional magnetic resonance imaging while performing an intertemporal choice task consisting of 40 sets of monetary reward options that varied by delay to delivery. Smokers were investigated in a state of nicotine satiation. Non‐smokers were investigated twice, receiving nicotine (2 mg) and placebo gums in a double‐blinded, randomized cross‐over design. Smokers displayed steeper temporal discounting than non‐smokers. Those behavioural differences were reflected in the brain response during the decision between two alternative money/time pairs: smokers showed less activation in parietal and occipital areas (e.g. precuneus) than non‐smokers under placebo. A single dose of nicotine in non‐smokers led to a similar effect on brain activation but did not impact behaviour. Processing of the reward magnitude of money/time pairs differed between smokers and non‐smokers: smokers showed decreased reactivity of the ventral striatum. Moreover, there was an acute nicotine effect in non‐smokers on processing of the reward magnitude: nicotine increased the correlation of blood oxygen level‐dependent response and mean amount in the left hippocampus, amygdala and anterior insula. We conclude that cross‐sectional differences between smokers and non‐smokers are only, in part, due to the acute pharmacological effects of nicotine. Longitudinal studies are needed to investigate pre‐drug group characteristics as well as consequences of smoking on discounting behaviour and its neural correlates.

Nicotine increases neural response to unpleasant stimuli and anxiety in non-smokers.

Studies in smokers suggest that nicotine might exert anxiolytic, stress‐dampening and mood‐enhancing effects and beneficially influences neural processing of affective information. Regarding non‐smokers, results are inconsistent, and no data exist on the effect of nicotine on neural emotion processing. We applied functional magnetic resonance imaging (fMRI) to assess the influence of nicotine on brain activation during processing of emotional stimuli in 31 non‐smokers with a maximum lifetime cigarette consumption of 20 cigarettes. Participants were subjected to two fMRI scans with event‐related presentations of images taken from the International Affective Picture System, receiving nicotine (2 mg) and placebo gums in a double‐blinded, randomized cross‐over design. Furthermore, subjective affect was assessed. Nicotine increased brain activity in response to unpleasant stimuli in the amygdala, anterior cingulate cortex (ACC) and basal ganglia, whereas processing of pleasant stimuli was not altered. Psychophysiological interaction (PPI) analyses revealed that nicotine increased connectivity between the amygdala and the perigenual ACC (pACC) during processing of unpleasant stimuli and decreased connectivity between those structures during processing of pleasant stimuli. Participants reported higher state anxiety under nicotine than placebo. A single dose of nicotine acted as a stressor in non‐smokers, leading to increased anxiety and neural activation elicited by unpleasant stimuli as well as altered connectivity within the amygdala–pACC circuit. Besides the possibility that reactions to nicotine may differ between non‐smokers and smokers due to tolerance and neuroadaptive processes that occur during prolonged nicotine use, a priori differences in smokers and non‐smokers might potentially explain diverse effects of nicotine on affect and emotional reactivity.

The personality trait self-directedness predicts the amygdala’s reaction to appetizing cues in fMRI☆

Personality and neural response to food cues in various mesolimbic brain structures have been linked to eating disorders. We investigated the question of whether personality traits in healthy individuals correlate with the brain activation induced on confrontation with appetizing visual stimuli. Personality was assessed in 27 normal-weight participants (14 women, mean age=26.0, SD=3.3 years) with the Temperament and Character Inventory (TCI). After an overnight fast, participants viewed blocks of pictures, half containing appetizing food and the other half showing scrambled pictures as control. After each block, participants rated their appetite. Brain activation was measured using a 3T MR scanner. Food compared to control stimuli elicited a significantly higher appetite rating, as well as strong activation in the ventral and dorsal visual stream, the fusiform gyrus and consecutive limbic centres such as the parahippocampal gyrus, the amygdala, the thalamus, the insula, the ventral striatum and the orbitofrontal cortex. In a region-of-interest analysis, the TCI trait self-directedness was negatively correlated with mean blood oxygenation level dependent (BOLD) signal change in the right amygdala (r=-.43, p=.025). Ultimately, amygdala reactivity might provide a risk factor for the development of eating disorders.

Human dopamine receptor D2/D3 availability predicts amygdala reactivity to unpleasant stimuli

Dopamine (DA) modulates the response of the amygdala. However, the relation between dopaminergic neurotransmission in striatal and extrastriatal brain regions and amygdala reactivity to affective stimuli has not yet been established. To address this issue, we measured DA D2/D3 receptor (DRD2/3) availability in twenty‐eight healthy men (nicotine‐dependent smokers and never‐smokers) using positron emission tomography with [18F]fallypride. In the same group of participants, amygdala response to unpleasant visual stimuli was determined using blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging. The effects of DRD2/3 availability in emotion‐related brain regions and nicotine dependence on amygdala response to unpleasant stimuli were examined by multiple regression analysis. We observed enhanced prefrontal DRD2/3 availability in those individuals with higher amygdala response to unpleasant stimuli. As compared to never‐smokers, smokers showed an attenuated amygdala BOLD response to unpleasant stimuli. Thus, individuals with high prefrontal DRD2/3 availability may be more responsive toward aversive and stressful information. Through this mechanism, dopaminergic neurotransmission might influence vulnerability for affective and anxiety disorders. Neuronal reactivity to unpleasant stimuli seems to be reduced by smoking. This observation could explain increased smoking rates in individuals with mental disorders. Hum Brain Mapp, 2010.